芯片上构建全结构无支架的血管化肾小管

IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL
Yuntian Zhu, Zhengdi Shi, Weiping Ding, Chengpan Li
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引用次数: 0

摘要

肾小管芯片已成为一种很有前途的药物肾毒性测试平台。然而,报道的肾小管芯片很难复制肾小管的独特结构,近端和远端小管较厚,Henle环较薄。在这项研究中,我们在微流控芯片上开发了一个结构完整的无支架的血管化肾小管。在芯片上,将两端粗段、中间细段的肾上皮细胞负载的海藻酸钙中空管u形包埋于胶原水凝胶中,与内皮细胞负载的海藻酸钙中空管平行,管径均匀。藻酸盐管在芯片上降解后,肾上皮细胞和内皮细胞自动附着于胶原水凝胶并增殖,形成具有近端小管、Henle环和远端小管的肾小管以及小管周围血管。我们评估细胞在中空海藻酸管上的活力,表征海藻酸管降解前后细胞的分布和形态,并从芯片上ATP合成、纤维连接蛋白分泌、VEGFR2表达等方面证实细胞的增殖和细胞的代谢功能。初步证实肾上皮细胞和内皮细胞代谢功能增强。本研究为在微流控芯片上设计更仿生的肾小管提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

On-chip construction of a fully structured scaffold-free vascularized renal tubule

On-chip construction of a fully structured scaffold-free vascularized renal tubule

Renal tubule chips have emerged as a promising platform for drug nephrotoxicity testing. However, the reported renal tubule chips hardly replicate the unique structure of renal tubules with thick proximal and distal tubules and a thin loop of Henle. In this study, we developed a fully structured scaffold-free vascularized renal tubule on a microfluidic chip. On the chip, the renal epithelial cell-laden hollow calcium-polymerized alginate tube with thick segments at both ends and a thin middle segment was U-shaped embedded in collagen hydrogel, parallel to the endothelial cell-laden hollow calcium-polymerized alginate tube with uniform tube diameter. After the alginate tubes were on-chip degraded, the renal epithelial cells and endothelial cells automatically attached to the collagen hydrogel and proliferated to form the renal tubule with proximal tubule, loop of Henle and distal tubule as well as peritubular blood vessel. We evaluated the viability of cells on the hollow alginate tubes, characterized the distribution and morphology of cells before and after the degradation of the alginate tube, and confirmed the proliferation of cells and the metabolic function of cells in terms of ATP synthesis, fibronectin secretion and VEGFR2 expression on the chip. The enhanced metabolic functions of renal epithelial cells and endothelial cells were preliminarily demonstrated. This study provides new insights into designing a more biomimetic renal tubule on a microfluidic chip.

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来源期刊
Biomedical Microdevices
Biomedical Microdevices 工程技术-工程:生物医学
CiteScore
6.90
自引率
3.60%
发文量
32
审稿时长
6 months
期刊介绍: Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology. General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules. Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.
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